Abstract

In mice, differential regulation of CXC chemokine receptor expression in circulating polymorphonuclear neutrophils (PMNs) undergoing senescence results in homing to the bone marrow. However, the role of this compartment and of the chemokine receptor
CXCR4 is still under discussion, and only scarce data exist about CXCR4 function in
human PMN. In our study, we provide evidence that also in human neutrophils, expression
(cell surface and mRNA), chemotactic and signaling functions of the homing-related
chemokine receptor CXCR4 are upregulated during aging in vitro, independent of addition
of stimulatory cytokines (TNF, IL-1, IL-8, G-CSF). In contrast, interleukin-8 receptors are
downmodulated (CXCR2) or remain unchanged (CXCR1), suggesting that human PMNs
undergoing senescence acquire a phenotype that impairs inflammatory extravasation and
favors homing to the bone marrow or other tissues involved in sequestration. Partially
retained responsiveness to interleukin-8 may be important for neutrophil function when
senescence occurs after extravasation in inflamed tissues.